Development of pro-inflammatory phenotype in monocytes after engulfing Hb-activated platelets in hemolytic disorders.
Clin Immunol
; 175: 133-142, 2017 02.
Article
em En
| MEDLINE
| ID: mdl-28039017
ABSTRACT
Monocytes and macrophage combat infections and maintain homeostatic balance by engulfing microbes and apoptotic cells, and releasing inflammatory cytokines. Studies have described that these cells develop anti-inflammatory properties upon recycling the free-hemoglobin (Hb) in hemolytic conditions. While investigating the phenotype of monocytes in two hemolytic disorders-paroxysmal nocturnal hemoglobinuria (PNH) and sickle cell disease (SCD), we observed a high number of pro-inflammatory (CD14+CD16hi) monocytes in these patients. We further investigated in vitro the phenotype of these monocytes and found an estimated 55% of CD14+ cells were transformed into the CD14+CD16hi subset after engulfing Hb-activated platelets. The CD14+CD16hi monocytes, which were positive for both intracellular Hb and CD42b (platelet marker), secreted significant amounts of TNF-α and IL-1ß, unlike monocytes treated with only free Hb, which secreted more IL-10. We have shown recently the presence of a high number of Hb-bound hyperactive platelets in patients with both diseases, and further investigated if the monocytes engulfed these activated platelets in vivo. As expected, we found 95% of CD14+CD16hi monocytes with both intracellular Hb and CD42b in both diseases, and they expressed high TNF-α. Furthermore our data showed that these monocytes whether from patients or developed in vitro after treatment with Hb-activated platelets, secreted significant amounts of tissue factor. Besides, these CD14+CD16hi monocytes displayed significantly decreased phagocytosis of E. coli. Our study therefore suggests that this alteration of monocyte phenotype may play a role in the increased propensity to pro-inflammatory/coagulant complications observed in these hemolytic disorders-PNH and SCD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
/
Hemoglobinas
/
Monócitos
/
Hemoglobinúria Paroxística
/
Inflamação
/
Anemia Falciforme
Limite:
Humans
Idioma:
En
Revista:
Clin Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Índia